Cytokines are proteins secreted by a cell of the immune system and transduce a signal to a specific cell. Cytokines have various kinds, and many of them are especially associated with immunity and inflammation and also associated with cell growth, cell differentiation, cell death, wound healing and the like (Curr Opin Cell Biol. 1991 April; 3(2):171-5).
The janus kinase (JAK) family plays a role in cytokine-dependent regulation of the function of cells associated with growth and immune response. JAK family consists of four kinds of janus kinases (JAK1 (janus kinase 1), JAK2 (janus kinase 2), JAK3 (janus kinase 3) and TYK2 (tyrosine kinase 2)). Among them, JAK1 is known to be involved in signal transduction of cytokines such as IL(interleukin)-2, IL-4, IL-7, IL-15, IL-21, IL-6, OSM (oncostatin M), IL-10 family, IFN(interferon)-α, IFN-β, IFN-γ and the like (Nature Immunology 10, 356-360 (2009)). TYK2 is known to be involved in signal transduction of cytokines such as IFN-α, IFN-β, IL-6, IL-10 family (IL-10, IL-19, IL-20, IL-22, IL-28, IL-29), IL-12, IL-23 and the like (Nature Immunology 10, 356-360 (2009), New York Academy of Science 1246, 34-40 (2011)). In addition, these cytokines play an important role in immune response when exist in an appropriate amount. However, excessive production of them is involved in many autoimmune diseases such as rheumatoid arthritis, psoriasis, inflammatory bowel disease, Sjogren's syndrome, Behcet's disease, multiple sclerosis, systemic lupus erythematosus and the like (Journal of Allergy and Clinical Immunology 127, 3, 701-721.e70 (2011), Cytokine & Growth Factor Reviews 19, 41-52 (2008), Invest Ophthalmol Vis Sci. 2008 July; 49(7):3058-3064, Ann Rheum Dis. 2010 July; 69(7):1325-1328).
Tocilizumab, which is an anti-IL-6 receptor monoclonal antibody, has been approved as a therapeutic drug for rheumatoid arthritis in Japan and Europe, and furthermore, clinical trials for various diseases in which the IL-6 signaling pathway is suggested to be involved are performed. From the foregoing, a JAK1 inhibitor can be a therapeutic drug for various autoimmune diseases such as rheumatoid arthritis, psoriasis, inflammatory bowel disease, Sjogren's syndrome, Behcet's disease, multiple sclerosis, systemic lupus erythematosus and the like (Clinical Science 122, 143-159 (2012)).
Moreover, JAK signal is also associated with differentiation and growth of various cancer cell (Trends Biochem. Sci. 33, 122-131 (2008)). Particularly, JAK1 is associated with leukemia and uterine leiomyosarcoma due to the constant activation therein (J Exp Med 205, 751-758 (2008), Oncogene 25, 4016-4026, (2006)). In addition, clinical trials of antibody and low molecule compound which target at IL-6 are performed for cancer diseases such as prostate cancer, multiple myeloma, cachexia, myelofibrosis and the like (Clinical Science 122, 143-159 (2012), The New England Journal of Medicine 363, 1117-1127 (2010)). From the foregoing, a JAK1 inhibitor can be a therapeutic drug for cancer diseases such as leukemia, uterine leiomyosarcoma, prostate cancer, multiple myeloma, cachexia, myelofibrosis and the like.
Ustekinumab, which is an anti-IL-12/23 monoclonal antibody, has been approved as a therapeutic drug for moderate to severe psoriasis patient in Europe, and furthermore, clinical trials for various diseases in which the IL-12/23 signaling pathway is suggested to be involved are performed. From the foregoing, a TYK2 inhibitor can be a therapeutic drug for various autoimmune diseases such as rheumatoid arthritis, psoriasis, inflammatory bowel disease, Sjogren's syndrome, Behcet's disease, multiple sclerosis, systemic lupus erythematosus and the like (Front Biosci. 2011 Jun. 1; 17:3214-32).
Examples of the compound having a structure similar to the compound described in the present specification include the following compounds.
(1) A compound represented by the following formula:
whereinR1 is H, aryl or the like;G is H or halogen;X, Y and Z are each independently C or N;A and B are each independently C or N;E is a bond, —CH2— or the like;D is —CR5R6—;R5 is trifluoromethyl;R6 is hydroxy or H; andR3 is an optionally substituted heteroaryl or the like,which is a glucocorticoid receptor modulator, and is useful for the treatment of sex hormone-dependent disease (prostatic hyperplasia, uterus myopathy, etc.) and the like (Patent Document 1).(2) A compound represented by the following formula:
whereinR1 is a formula —(CO)h—(NRa)—(CRb═CRc)k—Ar
wherein
Ra, Rb and Re are each independently H, —OH or the like; and
h, j and k are each independently 0-1;
Cy is an optionally substituted 5-6-membered aromatic heterocyclic group; and
V is -L-X—Y
wherein
L is a bond, C1-6 alkylene or the like;
X is a bond, —O—, —CO— or the like; and
Y is H, NO or the like,
which is a JNK inhibitor, and is useful for the treatment of Alzheimer's disease and the like, and
    3-(3-fluorophenyl)-1-trityl-1,5-dihydro-4H-pyrazolo[4,3-c]pyridin-4-one (Patent Document 2).(3) A compound represented by the following formula:
whereinR1 is H, —OH or the like;l is 1-2;R2 is H, nitro or acetylamino; andX is O or S,which is a cardiac stimulant (Patent Document 3).(4) A production method represented by the following formula:
whereinR1 is H, halogen or the like; andR2 is H, alkyl or phenyl,(Patent Document 4).(5) A compound represented by the following formula:
whereinR1, R2, R3 and R4 are each independently C1-8 alkyl, C1-8 hetero alkyl or the like;R5 and R6 are each independently C1-8 alkyl, C1-8 hetero alkyl or the like;R1, R2, R3, R4, R5 and R6 optionally form a 5-10-membered ring;Ring A is an optionally substituted 5-membered aromatic heterocycle or the like;Ring N is an optionally substituted 6-membered aromatic heterocycle or the like;Ar is an optionally substituted 5-10-membered aryl or an optionally substituted 5-10-membered heteroaryl;m and n are each independently 1-6; andp is 0-1,which is a CXCR4 inhibitor, and is useful for the treatment of rheumatoid arthritis and the like (Patent Document 5).(6) A compound represented by the following formula:
whereinW is CH or N;Ring B is an optionally substituted 5-6-membered aromatic heterocycle;R1 is an optionally substituted aryl or the like; and Ring A is an optionally substituted 5-membered nitrogen-containing aromatic heterocycle,which is a JAK (JAK1, JAK2, JAK3, TYK2) inhibitor, and is useful for the treatment of rheumatism, psoriasis and the like (Patent Document 6).(7) A compound represented by the following formula:
whereinR2 and R3 are each independently H or C1-6 alkyl, (Patent Document 7).(8) A compound represented by the following formula:

R1 
26 methyl
27 phenyl
28 2-pyridyl
29 4-methoxyphenyl
30 3-methoxyphenyl
31 4-(4-methylpiperazin-1-yl)-phenyl
32 piperidin-4-yl.
which is an inhibitor of kinase such as CDK, GSK3β and the like, and is useful for the treatment of cancer and the like (Non-Patent Document 1).
(9) A compound represented by the following formula:
(Non-Patent Document 2).(10) A compound represented by the following formula:
(Non-Patent Document 3).(11) The following compounds are disclosed in Chemical Abstract.1) Registry Number: 30081-66-4
2) Registry Number: 30081-67-5
3) Registry Number: 143035-29-4
4) Registry Number: 143035-23-8
5) Registry Number: 13945-10-3
6) Registry Number: 143035-24-9
7) Registry Number: 143035-25-0
8) Registry Number: 143035-26-1
9) Registry Number: 143035-27-2
10) Registry Number: 143035-30-7
11) Registry Number: 143035-31-8
12) Registry Number: 143035-32-9
13) Registry Number: 143035-33-0
14) Registry Number: 143035-34-1
15) Registry Number: 143035-28-3
16) Registry Number: 143035-35-2
17) Registry Number: 143035-36-3
18) Registry Number: 30081-66-4
19) Registry Number: 30081-67-5
20) Registry Number: 32460-25-6
21) Registry Number: 30081-66-4
22) Registry Number: 30081-67-5
23) Registry Number: 13945-10-3
24) Registry Number: 13945-11-4
25) Registry Number: 13945-12-5
26) Registry Number: 13945-13-6
27) Registry Number: 14033-34-2
28) Registry Number: 14633-09-1
29) Registry Number: 958795-03-4
